Citicoline Restores Endoplasmic Reticulum Homeostasis by Regulating Oxidative Stress Through CDO1 to Reverse Myopia Progression

Objective: To investigate whether citicoline alleviates endoplasmic reticulum (ER) stress by modulating oxidative stress in myopia. Results: A form-deprivation myopia model in guinea pigs and a hypoxia-induced model in human scleral fibroblasts revealed that citicoline downregulated cysteine dioxygenase 1 (CDO1) expression, increased glutathione, and reduced reactive oxygen species. These changes mitigated oxidative stress, suppressed ER stress, maintained cellular homeostasis, and inhibited extracellular matrix remodeling, leading to reduced axial elongation. Innovation: Transcriptomic profiling identified CDO1 as a novel downstream effector of citicoline, linking cysteine metabolism to oxidative and ER stress regulation in myopia. Conclusion: Citicoline shows potential to delay myopia progression by alleviating ER stress through CDO1-mediated redox regulation, providing preclinical mechanistic insight into its possible role in myopia control. Antioxid. Redox Signal. 45, 113–132.